gms | German Medical Science

Objective: Vestibular schwannomas (VS) are the most common tumors of the cerebellopontine angle. Typical symptoms are vertigo, tinnitus, hearing loss and facial nerve paresis. Beside scan and wait, current therapeutic strategies are limited to tumor resection and/or radiotherapy. The molecular differences of progressive or stagnating VS are unknown. Evidence suggested that increased vascularization, secretion of macrophage activating factors or enhanced expression of inflammation or growth factors may play a role. Based on these findings, comparative expression analyses of VS with different growth characteristics and Koos classification were performed to identify tumor markers in an explorative study.

Methods: RNA was isolated from VS tissue of 141 patients with different Koos classification. Excluded were patients with neurofibromatosis, previously irradiated VS and recurrences. The mRNA was transcribed into cDNA and the expression of monocytic markers CD68, CD163 and macrophage colony-stimulating factor (M-CSF) was determined using qPCR. In addition, the transcript level of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX2) and Ki-67 (proliferation) was measured. The relationship between marker expression, tumor cell proliferation and Koos classification was tested using the Spearman’s rank correlation coefficient, respectively.

Results: The data analysis showed a strong positive correlation of the inflammation markers CD68 and CD163 (r=0.71, p<0.0001). A moderate positive correlation was detected both between M-CSF with CD163 (r=0.48, p<0.0001) and CD68 (r=0.47, p<0.0001) as well as between the vasculatory factor VEGF and the proliferation marker Ki-67 (r=0.42, p<0.0001). Surprisingly, a weak negative correlation between the Koos classification and proliferation (Ki-67, r=-0.39, p<0.0001; COX2, r=-0.32, p=0.0001) and vacularisation (VEGF, r=-0.26, p=0.002) was found. In contrast, a weak positive correlation of the Koos classification with the inflammatory markers CD68 (r=0.35, p=0.0001) and CD163 (r=0.21, p=0.02) as well as between Ki-67 and M-CSF (r=0.23, p=0.0072) was observed.

Conclusion: The initial explorative data of our study suggest that VS with low Koos grade have higher expression of proliferation markers, whereas higher Koos grades show increased expression of inflammatory and macrophage markers. Therefore, it seems that the progression of VS is not only driven by proliferation, but could be induced by macrophage infiltration and inflammatory processes.